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Severe anaphylactic reactions to neuromuscular blocking agents, including NUROMAX (doxacurium chloride) , have been reported. These reactions have in some cases been life-threatening and fatal. Due to the potential severity of these reactions, the necessary precautions, such as the immediate availability of appropriate emergency treatment, should be taken. Precautions should also be taken in those individuals who have had previous anaphylactic reactions to other neuromuscular blocking agents since cross-reactivity between neuromuscular blocking agents, both depolarizing and non-depolarizing, has been reported in this class of drugs.
NUROMAX (doxacurium chloride) SHOULD BE ADMINISTERED IN CAREFULLY ADJUSTED DOSAGE BY OR UNDER THE SUPERVISION OF EXPERIENCED CLINICIANS WHO ARE FAMILIAR WITH THE DRUG'S ACTIONS AND THE POSSIBLE COMPLICATIONS OF ITS USE. THE DRUG SHOULD NOT BE ADMINISTERED UNLESS FACILITIES FOR INTUBATION, ARTIFICIAL RESPIRATION, OXYGEN THERAPY, AND AN ANTAGONIST ARE WITHIN IMMEDIATE REACH. IT IS RECOMMENDED THAT CLINICIANS ADMINISTERING LONG-ACTING NEUROMUSCULAR BLOCKING AGENTS SUCH AS NUROMAX (doxacurium chloride) EMPLOY A PERIPHERAL NERVE STIMULATOR TO MONITOR DRUG RESPONSE, NEED FOR ADDITIONAL RELAXANTS, AND ADEQUACY OF SPONTANEOUS RECOVERY OR ANTAGONISM.
NUROMAX (doxacurium chloride) HAS NO KNOWN EFFECT ON CONSCIOUSNESS, PAIN THRESHOLD, OR CEREBRATION. TO AVOID DISTRESS TO THE PATIENT, NEUROMUSCULAR BLOCK SHOULD NOT BE INDUCED BEFORE UNCONSCIOUSNESS.
NUROMAX (doxacurium chloride) Injection is acidic (pH 3.9 to 5.0) and may not be compatible with alkaline solutions having a pH greater than 8.5 (e.g., barbiturate solutions).
NUROMAX (doxacurium chloride) Injection contains benzyl alcohol, which is potentially toxic when administered locally to neural tissue. Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources (see WARNINGS and PRECAUTIONS: Pediatric Use).
NUROMAX (doxacurium chloride) has no clinically significant effects on heart rate; therefore, NUROMAX (doxacurium chloride) will not counteract the bradycardia produced by many anesthetic agents or by vagal stimulation.
Neuromuscular blocking agents may have a profound effect in patients with neuromuscular diseases (e.g., myasthenia gravis and the myasthenic syndrome). In these and other conditions in which prolonged neuromuscular block is a possibility (e.g., carcinomatosis), the use of a peripheral nerve stimulator and a small test dose of NUROMAX (doxacurium chloride) are recommended to assess the level of neuromuscular block and to monitor dosage requirements. Shorter acting muscle relaxants than NUROMAX (doxacurium chloride) may be more suitable for these patients.
Resistance to nondepolarizing neuromuscular blocking agents may develop in patients with burns depending upon the time elapsed since the injury and the size of the burn. NUROMAX (doxacurium chloride) has not been studied in patients with burns.
Acid-base and/or serum electrolyte abnormalities may potentiate or antagonize the action of neuromuscular blocking agents. The action of neuromuscular blocking agents may be enhanced by magnesium salts administered for the management of toxemia of pregnancy.
NUROMAX (doxacurium chloride) has not been studied in patients with asthma.
No data are available to support the use of NUROMAX (doxacurium chloride) by intramuscular injection.
Since allergic cross-reactivity has been reported in this class, request information from your patients about previous anaphylactic reactions to other neuromuscular blocking agents. In addition, inform your patients that severe anaphylactic reactions to neuromuscular blocking agents, including NUROMAX have been reported (see CONTRAINDICATIONS).
Renal and Hepatic Disease
NUROMAX (doxacurium chloride) has been studied in patients with end-stage kidney (n = 8) or liver (n = 7) disease undergoing transplantation procedures (see CLINICAL PHARMACOLOGY). The possibility of prolonged neuromuscular block in patients undergoing renal transplantation and the possibility of a variable onset and duration of neuromuscular block in patients undergoing liver transplantation must be considered when NUROMAX (doxacurium chloride) is used in such patients.
Administration of NUROMAX (doxacurium chloride) on the basis of actual body weight is associated with a prolonged duration of action in obese patients (patients weighing ≥ 30% more than ideal body weight for height) (see CLINICAL PHARMACOLOGY). Therefore, the dose of NUROMAX (doxacurium chloride) should be based upon ideal body weight in obese patients (see CLINICAL PHARMACOLOGY - Individualization of Dosages).
Malignant Hyperthermia (MH)
In a study of MH-susceptible pigs, NUROMAX (doxacurium chloride) did not trigger MH. NUROMAX (doxacurium chloride) has not been studied in MH-susceptible patients. Since MH can develop in the absence of established triggering agents, the clinician should be prepared to recognize and treat MH in any patient scheduled for general anesthesia.
Long-Term Use in the Intensive Care Unit (ICU)
Information on the use of NUROMAX (doxacurium chloride) in the ICU is limited. In a double-blind, randomized study, 17 patients received NUROMAX (doxacurium chloride) by intermittent bolus injection for a mean of 2.7 ± 0.5 days (range: 0.8 to 6.8 days) to facilitate mechanical ventilation. No evidence of tachyphylaxis, accumulation, or prolonged recovery was observed. The adverse experiences in patients receiving NUROMAX (doxacurium chloride) were consistent in type, severity, and frequency to those expected in a critically ill patient population. Since many ICU patients have hepatic and/or renal failure, a prolonged duration of block should be anticipated in these patients after administration of NUROMAX (doxacurium chloride) .
WHENEVER THE USE OF NUROMAX (doxacurium chloride) OR ANY NEUROMUSCULAR BLOCKING AGENT IS CONTEMPLATED IN THE ICU, IT IS RECOMMENDED THAT NEUROMUSCULAR TRANSMISSION BE MONITORED CONTINUOUSLY DURING ADMINISTRATION WITH THE HELP OF A NERVE STIMULATOR. ADDITIONAL DOSES OF NUROMAX (doxacurium chloride) OR ANY OTHER NEUROMUSCULAR BLOCKING AGENT SHOULD NOT BE GIVEN BEFORE THERE IS A DEFINITE RESPONSE TO T1, OR TO THE FIRST TWITCH. IF NO RESPONSE IS ELICITED, BOLUS ADMINISTRATION SHOULD BE DELAYED UNTIL A RESPONSE RETURNS.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis and fertility studies have not been performed. NUROMAX (doxacurium chloride) was evaluated in a battery of four short-term mutagenicity tests. It was nonmutagenic in the Ames Salmonella assay, in the mouse lymphoma assay, and in the human lymphocyte assay. In the in vivo rat bone marrow cytogenetic assay, statistically significant increases in the incidence of structural abnormalities, relative to vehicle controls, were observed in male rats dosed with 0.1 mg/kg (0.625 mg/m²) NUROMAX (doxacurium chloride) and sacrificed at 6 hours, but not at 24 or 48 hours, and in female rats dosed with 0.2 mg/kg (1.25 mg/m²) NUROMAX (doxacurium chloride) and sacrificed at 24 hours, but not at 6 or 48 hours. There was no increase in structural abnormalities in either male or female rats given 0.3 mg/kg (1.875 mg/m²) NUROMAX (doxacurium chloride) and sacrificed at 6, 24, or 48 hours. Thus, the incidence of abnormalities in the in vivo rat bone marrow cytogenetic assay was not dose-dependent and, therefore, the likelihood that the observed abnormalities were treatment-related or clinically significant is low.
Teratogenic Effect - Pregnancy Category C
Teratology testing in nonventilated, pregnant rats and mice treated subcutaneously with maximum subparalyzing doses of NUROMAX (doxacurium chloride) revealed no maternal or fetal toxicity or teratogenic effects. There are no adequate and well-controlled studies of NUROMAX (doxacurium chloride) in pregnant women. Because animal studies are not always predictive of human response and the doses used were subparalyzing, NUROMAX (doxacurium chloride) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Labor and Delivery
The use of NUROMAX (doxacurium chloride) during labor, vaginal delivery, or cesarean section has not been studied. It is not known whether NUROMAX (doxacurium chloride) administered to the mother has immediate or delayed effects on the fetus. The duration of action of NUROMAX (doxacurium chloride) exceeds the usual duration of operative obstetrics (cesarean section). Therefore, NUROMAX (doxacurium chloride) is not recommended for use in patients undergoing C-section.
It is not known whether NUROMAX (doxacurium chloride) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised following administration of NUROMAX (doxacurium chloride) to a nursing woman.
NUROMAX (doxacurium chloride) has not been studied in pediatric patients below the age of 2 years. See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION for clinical experience and recommendations for use in children 2 to 12 years of age. This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome”, (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages > 99 mg/kg/day in neonates and low-birthweight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
Of the total number of subjects in the clinical studies of NUROMAX (doxacurium chloride) , 134 were 60 years of age and over while 37 were 70 years of age and over. The geriatric population included a subset of patients with significant cardiovascular disease. The clearance of doxacurium may be reduced and the half-life may be prolonged in elderly patients. In addition, the onset of maximum block is slower and the duration of neuromuscular block produced by NUROMAX (doxacurium chloride) is more variable and, in some cases, longer than in young adult patients (see CLINICAL PHARMACOLOGY - Pharmacodynamics and Individualization of Dosages).
This drug is known to be excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/4/2011
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